Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, 71069Zhejiang University School of Medicine, Hangzhou, China.
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Technol Cancer Res Treat. 2022 Jan-Dec;21:15330338221106820. doi: 10.1177/15330338221106820.
Chloride intracellular channel 1 (CLIC1) is upregulated in hepatocellular carcinoma (HCC). The present study aimed to investigate the role of CLIC1 in HCC angiogenesis. Immunohistochemistry (IHC) was used to test the expression of CLIC1 and CD34 in 67 pairs of HCC and paracarcinoma tissues. The prognosis data of the patients were used to analyze the clinical relevance of CLIC1. We built a coculture system of HCC cells and endothelial cells to explore the migration of endothelial cells. Conditioned media (CMs) from HCC cells was then collected to assess endothelial cell migration. Experiments were then conducted to confirm the relationship between CLIC1 and angiogenesis in a subcutaneous tumor model. CLIC1 expression was higher in HCC tumor tissues than in paracarcinoma tissues. Patients with increased CLIC1 expression showed a higher microvascular density (MVD; = .013). Kaplan-Meier curves indicated that patients with lower expression of CLIC1 had better overall survival ( < .001) and recurrence-free survival ( = .046). Vascular endothelial growth factor A (VEGFA) in CMs from CLIC1-knockdown cells was lower than in the control group, while VEGFA in CMs from CLIC1 overexpression cells was higher than in the control group. CMs from CLIC1 overexpression cell lines promote the in vitro migration of EA.hy926 cells. Meanwhile, adding Bevacizumab to CMs from CLIC1 overexpression cells significantly inhibited this migration. The growth of xenograft tumors derived from CLIC1-knockdown Huh7 cells was restrained compared with the control group ( < .001). IHC staining showed MVD was higher in tumors with CLIC1 overexpression. CLIC1 is a promising biomarker for predicting the prognosis of HCC patients, and expression of CLIC1 correlates with angiogenesis in HCC through regulating VEGFA.
氯离子通道蛋白 1（CLIC1）在肝细胞癌（HCC）中上调。本研究旨在探讨 CLIC1 在 HCC 血管生成中的作用。免疫组织化学（IHC）用于检测 67 对 HCC 和癌旁组织中 CLIC1 和 CD34 的表达。利用患者的预后数据分析 CLIC1 的临床相关性。我们构建了 HCC 细胞和内皮细胞的共培养体系，以探讨内皮细胞的迁移。然后收集 HCC 细胞的条件培养基（CMs）来评估内皮细胞的迁移。然后在皮下肿瘤模型中进行实验以确认 CLIC1 与血管生成之间的关系。CLIC1 在 HCC 肿瘤组织中的表达高于癌旁组织。CLIC1 表达增加的患者微血管密度（MVD）更高（=.013）。Kaplan-Meier 曲线表明，CLIC1 表达较低的患者总生存期（<.001）和无复发生存期（=.046）更好。CLIC1 敲低细胞的 CMs 中的血管内皮生长因子 A（VEGFA）低于对照组，而 CLIC1 过表达细胞的 CMs 中的 VEGFA 高于对照组。CLIC1 过表达细胞系的 CMs 促进 EA.hy926 细胞的体外迁移。同时，向 CLIC1 过表达细胞的 CMs 中添加 Bevacizumab 可显著抑制这种迁移。与对照组相比，CLIC1 敲低 Huh7 细胞来源的异种移植肿瘤的生长受到抑制（<.001）。IHC 染色显示，CLIC1 过表达的肿瘤中 MVD 更高。CLIC1 是预测 HCC 患者预后的有前途的生物标志物，其表达通过调节 VEGFA 与 HCC 中的血管生成相关。
